The research proposed in this project is directed toward elucidating events which control beta-adrenergic receptor function, both at the biochemical and tissue level. The question of whether a direct functional relationship exists between beta receptors and adenylate cyclase in cardiac contractility will be examined by 1) assessing synthesis patterns of the beta-receptor and adenylate cyclase macromolecules during various stages of the cell cycle; 2) by characterization of cardiac beta receptors with radiolabeled adrenergic ligands and by determining the distribution of beta-adrenergic receptors and adenylate cyclase activity throughout principal areas of the myocardium. Purification of cell membrane fragments "enriched" with adrenergic receptors and of detergent solubilized beta-adrenergic receptors will be attempted utilizing affinity chromatography and affinity partitioning. The tissue sites of catecholamine action in cardiac muscle will investigate the relationship between adrenergic receptor occupancy, increase in cyclic AMP and the initiation of cardiac inotropic responses, by examining the response to catecholamines covalently immobilized on soluble amino acid polymers of varing molecular weight. The diffusion properties of these macromolecules provides the means of testing the above parameters by relating the fractional uptake of catecholamines to the extent of tissue activation (contractility and cyclic AMP).